The chronic use or abuse of barbiturates leads to drug dependence, and subsequent babiturate withdrawal results in a severe abstinence syndrome which in some cases may become life threatening. Clinicians have rated withdrawal from barbiturates as more severe than withdrawal from heroin or morphine. However, unlike morphine and ethanol which have been studied extensively almost no experimental information is available as to the effects of chronic barbiturate adminstration on the neurochemistry of putative neurotransmiters in the brain. Recent studies in my laboratory have shown that the turnover of noradrenaline (NA) is increased in the telencephalon and the brainstem of barbital dependent rats within 1 day following barbital withdrawal and remains elevated for at least 2 days after withdrawal. Dopamine (DA) content is also decreased in the telencephalons of these animals. On the other hand, brain serotonin (5-HT) is not affected by chronic barbital administration or subsequent withdrawal. Experiments outlined in this renewal proposal will investigate the effects of chronic barbital administration and/or subsequent withdrawal on principal NA and DA metabolites and on the sensitivity of NA and/or DA receptors. Pharmacological studies will explore the possible functional role that the changes in NA and DA content or turnover have in the expression of the barbiturate abstinence syndrome. In separate experiments DA and NA content and turnover will be investigated in chronic barbital treated male Swiss mice to determine the possible relationship of these amines to the increased intermale aggression observed in these animals. Later experiments will investigate the effects of chronic barbital administration on the brain levels of phenylethylamine, an orgotrophic neuromodulator, which could be responsible for some of the behavioral excitation observed in rats withdrawn from barbital or in chronic barbital treated Swiss mice. Information gained from these studies will be of use in the development of new therapeutic methods for the treatment of behavioral and neurological disorders associated with barbiturate dependence and withdrawal.